(1) The structure and distribution of a novel Mg-dependent, Ca- inhibitable protein phosphatase (CIPase) from bovine brain has been studied. Partial cDNA sequence of CIPase reveals that it is akin to another Mg-dependent, type 2C protein phosphotase (PP2C). CIPase activity was found in every mouse organ examined and its amount was about twice as much as PP2C, indicating that it is a major serine/threonine phosphatase. (2) Calmodulin-dependent kinase II and a calyculin A-inhibitable phosphatase are found to be key factors in sustaining calcium oscillations and regulating the frequency in HeLa cells. First evidence for in vivo phosphorylation of inositol trisphosphate receptor has been obtained. A theory for interpreting calcium oscillations in HeLa cells has been proposed. An "x factor" necessary for sustaining calcium spiking is found to be a derivative related to inositol-1,3,4,5- tetrakisphosphate. (3) Calcineurin, a calmodulin-dependent phosphatase previously identified as Zn and Fe-containing enzyme in this laboratory, was found by EPR and activity studies to require Fe(II) ion for catalysis. The Fe(III) form of calcineurin yielded EPR signal at a g factor of 4.3 and the line shapes are typical of the tetrahedral coordinates found in transferrin. But the Fe(III) enzyme form was inactive with p- nitrophenylphosphate as substrate.